Ozarelix, a fourth generation GnRH antagonist, induces apoptosis in hormone refractory androgen receptor negative prostate cancer cells modulating expression and activity of death receptors

The Prostate
C FestucciaMarcella Motta

Abstract

Antagonistic or agonistic analogues of gonadotropin-releasing hormone are extensively used for the treatment of advanced hormone-dependent prostate cancer. However, the majority of recurrent prostate tumors is androgen independent. This study explored the in vitro effects on DU145 and PC3 cell lines, two models of androgen-independent prostate cancer, of a fourth generation GnRH antagonist (Ozarelix). Ozarelix was added to cultures and toxicity, cell cycle modifications, cell viability and caspase activity were investigated. Ozarelix showed antiproliferative effects and produced an accumulation of cells in G2/M cell cycle phase. Apoptosis was related with caspase-8-dependent caspase 3 activation with down-regulation of c-FLIP (L) and a sensitization to TRAIL-induced apoptosis linked also to increased expression and activity of death receptors DR4/5 and Fas. TRAIL-resistant cancer cells can be sensitized to TRAIL by Ozarelix. This effect may be achieved by the activation of apoptotic pathway improving the therapeutic effects in androgen independent tumor cell lines. However, a better understanding of molecular mechanisms by which GnRH antagonists may act in androgen independent models is necessary.

References

Aug 1, 1988·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·B FeinbergJ U Gutterman
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·T YanoA V Schally
May 16, 1997·International Journal of Cancer. Journal International Du Cancer·M L KottlerR Counis
May 20, 1998·Cancer Treatment and Research·R L Bare, F M Torti
Aug 12, 1998·The Journal of Steroid Biochemistry and Molecular Biology·G EmonsK D Schulz
Oct 2, 1998·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·G von Minckwitz, M Kaufmann
Jul 27, 1999·Gynecologic Oncology·J H KimS E Namkoong
Sep 27, 2006·Anti-cancer Drugs·Tomasz M BeerUNKNOWN Abarelix Study Group
Jan 24, 2007·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Mar 11, 2008·Cancer Letters·Frank A E Kruyt
Nov 13, 2008·International Journal of Cancer. Journal International Du Cancer·Simone Fulda
Nov 15, 2008·Trends in Endocrinology and Metabolism : TEM·Ilpo HuhtaniemiBo-Eric Persson

❮ Previous
Next ❯

Citations

Sep 10, 2011·Therapeutic Advances in Urology·Laurent Boccon-GibodBo-Eric Persson
Feb 22, 2012·Cancers·Ahmad R Safa, Karen E Pollok
Jul 11, 2012·Endocrine Reviews·Patrizia LimontaRoberta M Moretti
Aug 23, 2017·Expert Opinion on Emerging Drugs·Dominique ThomasAlexis Te
Dec 18, 2020·International Journal of Molecular Sciences·Fabrizio FontanaPatrizia Limonta
Jul 2, 2021·Frontiers in Molecular Biosciences·Walter CabriAlessandra Tolomelli

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis